ICURE: Intensive care unit (ICU) risk evaluation for 30-day mortality. Developing and evaluating a multivariable machine learning prediction model for patients admitted to the general ICU in Sweden.

BACKGROUND: A prediction model that estimates mortality at admission to the intensive care unit (ICU) is of potential benefit to both patients and society. Logistic regression models like Simplified Acute Physiology Score 3 (SAPS 3) and APACHE are the traditional ICU mortality prediction models. With the emergence of machine learning (machine learning) and artificial intelligence, new possibilities arise to create prediction models that have the potential to sharpen predictive accuracy and reduce the likelihood of misclassification in the prediction of 30-day mortality. METHODS: We used the Swedish Intensive Care Registry (SIR) to identify and include all patients ≥18 years of age admitted to general ICUs in Sweden from 2008 to 2022 with SAPS 3 score registered. Only data collected within 1 h of ICU admission was used. We had 153 candidate predictors including baseline characteristics, previous medical conditions, blood works, physiological parameters, cause of admission, and initial treatment. We stratified the data randomly on the outcome variable 30-day mortality and created a training set (80% of data) and a test set (20% of data). We evaluated several hundred prediction models using multiple ML frameworks including random forest, gradient boosting, neural networks, and logistic regression models. Model performance was evaluated by comparing the receiver operator characteristic area under the curve (AUC-ROC). The best performing model was fine-tuned by optimizing hyperparameters. The model's calibration was evaluated by a calibration belt. Ultimately, we simplified the best performing model with the top 1-20 predictors. RESULTS: We included 296,344 first-time ICU admissions. We found age, Glasgow Coma Scale, creatinine, systolic blood pressure, and pH being the most important predictors. The AUC-ROC was 0.884 in test data using all predictors, specificity 95.2%, sensitivity 47.0%, negative predictive value of 87.9% and positive predictive value of 70.7%. The final model showed excellent calibration. The ICU risk evaluation for 30-day mortality (ICURE) prediction model performed equally well to the SAPS 3 score with only eight variables and improved further with the addition of more variables. CONCLUSION: The ICURE prediction model predicts 30-day mortality rate at first-time ICU admission superiorly compared to the established SAPS 3 score.

Intensive care unit-acquired infections more common in patients with COVID-19 than with influenza.

Intensive care unit-acquired infections are complicating events in critically ill patients. In this study we analyzed the incidence, microbiological patterns, and outcome in patients with COVID-19 versus influenza in the intensive care unit (ICU). We included all adult patients treated with invasive mechanical ventilation due to (1) COVID-19 between January 2020 and March 2022, and (2) influenza between January 2015 and May 2023 at Sahlgrenska University Hospital, Sweden. Of the 480 participants included in the final analysis, 436 had COVID-19. The incidence rates of ICU-acquired infections were 31.6/1000 and 9.9/1000 ICU-days in the COVID-19 and influenza cohorts, respectively. Ventilator-associated lower respiratory tract infections were most common in both groups. In patients with COVID-19, corticosteroid treatment was associated with an increased risk of ICU-acquired infections and with higher 90-day mortality in case of infection. Furthermore, ICU-acquired infection was associated with a prolonged time in the ICU, with more difficult-to-treat gram-negative infections in late versus early ventilator-associated lower respiratory tract infections. Further research is needed to understand how the association between corticosteroid treatment and incidence and outcome of ICU-acquired infections varies across different patient categories.

Global ischemia induces stemness and dedifferentiation in human adult cardiomyocytes after cardiac arrest.

Global ischemia has been shown to induce cardiac regenerative response in animal models. One of the suggested mechanisms behind cardiac regeneration is dedifferentiation of cardiomyocytes. How human adult cardiomyocytes respond to global ischemia is not fully known. In this study, biopsies from the left ventricle (LV) and the atrioventricular junction (AVj), a potential stem cell niche, were collected from multi-organ donors with cardiac arrest (N = 15) or without cardiac arrest (N = 6). Using immunohistochemistry, we investigated the expression of biomarkers associated with stem cells during cardiomyogenesis; MDR1, SSEA4, NKX2.5, and WT1, proliferation markers PCNA and Ki67, and hypoxia responsive factor HIF1α. The myocyte nuclei marker PCM1 and cardiac Troponin T were also included. We found expression of cardiac stem cell markers in a subpopulation of LV cardiomyocytes in the cardiac arrest group. The same cells showed a low expression of Troponin T indicating remodeling of cardiomyocytes. No such expression was found in cardiomyocytes from the control group. Stem cell biomarker expression in AVj was more pronounced in the cardiac arrest group. Furthermore, co-expression of PCNA and Ki67 with PCM1 was only found in the cardiac arrest group in the AVj. Our results indicate that a subpopulation of human cardiomyocytes in the LV undergo partial dedifferentiation upon global ischemia and may be involved in the cardiac regenerative response together with immature cardiomyocytes in the AVj.

Donor heart dysfunction and graft survival in liver and kidney transplants-A register-based study from Sweden.

BACKGROUND AND AIM: Stress cardiomyopathy in donors can potentially affect graft function and longevity. This study aims to investigate the association between echocardiographic left ventricular ejection fraction (LVEF) < 50%, and/or the presence of left ventricular regional wall motion abnormalities (RWMA) in organ donors, and short- and long-term liver and kidney graft survival. Our secondary aim was to link graft survival with donor and recipient characteristics. METHODS: All donors considered for liver and kidney donation with echocardiographic records at Sahlgrenska University Hospital between 2006 and 2016 were matched with their recipients through the Scandiatransplant register. The studied outcomes were graft survival, re-transplantation, and recipient death. Kaplan-Meier curves were used to plot time to event. Multivariate Cox-regression was used to test independence. RESULTS: There were 370 liver donors and 312 kidney donors (matched with 458 recipients) with echocardiographic records at Sahlgrenska University Hospital between June 2006 and November 2016. Of patients with LV dysfunction by echocardiography, there were 102 liver- and 72 kidney donors. Univariate survival analyses showed no statistical difference in the short- and long-term graft survival from donors with LV dysfunction compared to donors without. Donor age > 65 years, recipient re-transplantation and recipient liver tumor were predictors of worse outcome in liver transplants (p < .05). Donor age > 65, donor hypertension, recipient re-transplantation, and a recipient diagnosis of diabetes or nephritis/glomerulonephritis had a negative association with graft survival in kidney transplants (p < .05). CONCLUSION: We found no significant association between donor LV dysfunction and short- and long-term graft survival in liver and kidney transplants, suggesting that livers and kidneys from such donors can be safely transplanted.

High-sensitivity troponin T for detection of culprit lesions in patients with out-of-hospital cardiac arrest.

BACKGROUND: Patients with an out-of-hospital cardiac arrest (OHCA) often undergo coronary angiography, although a culprit lesion is found in only 30%-40% of patients. The aim of this study was to investigate high-sensitivity troponin T (hsTnT) levels in post cardiac arrest patients with and without coronary culprit lesions; factors affecting hsTnT levels after return of spontaneous circulation (ROSC); and the diagnostic ability of hsTnT in identifying patients with culprit lesions. We hypothesized that peak hsTnT levels were higher during the initial 48 h after cardiac arrest in patients with a coronary culprit lesion. METHODS: This was a retrospective observational study, which included patients admitted to the Intensive Care Unit after an OHCA and who received a coronary angiography. Peak values and dynamic changes in hsTnT were analyzed in relation to the presence of a culprit lesion at coronary angiography. RESULTS: A total of 238 patients were studied, of whom 140 had a culprit lesion. HsTnT levels during the initial 48 h were higher in patients with culprit lesions, longer time to ROSC and an unwitnessed cardiac arrest. At 6 to 12 h after ROSC, a hsTnT cut-off level of 1690 ng/L had a sensitivity of 64% and specificity of 84% to identify a culprit lesion. In patients without ST-elevations, hsTnT measured between 6 and 12 h after ROSC had a specificity above 90%, with a sensitivity of 46%. CONCLUSION: HsTnT levels after cardiac arrest are higher in patients with coronary culprit lesions. Presence of a culprit lesion, witnessed status and the duration of CPR are important factors affecting hsTnT levels. Repeated measurement of hsTnT within the first 12 h after admission improved diagnostic accuracy but the value of hsTnT as a predictor of culprit lesions early after OHCA is limited.

Survival of Critically Ill COVID-19 Patients in Sweden During the First Two and a Half Years of the Pandemic.

OBJECTIVES: Some studies have examined survival trends among critically ill COVID-19 patients, but most were case reports, small cohorts, and had relatively short follow-up periods. We aimed to examine the survival trend among critically ill COVID-19 patients during the first two and a half years of the pandemic and investigate potential predictors across different variants of concern periods. DESIGN: Prospective cohort study. SETTING: Swedish ICUs, between March 6, 2020, and December 31, 2022. PATIENTS: Adult COVID-19 ICU patients of 18 years old or older from the Swedish Intensive Care Register (SIR) that were linked to multiple other national registers. MEASUREMENT AND MAIN RESULTS: Survival probability and predictors of COVID-19 death were estimated using Kaplan-Meier and Cox regression analysis. Of 8975 patients, 2927 (32.6%) died. The survival rate among COVID-19 critically ill patients appears to have changed over time, with a worse survival in the Omicron period overall. The adjusted hazard ratios (aHRs) comparing older and younger ages were consistently strong but slightly attenuated in the Omicron period. After adjustment, the aHR of death was significantly higher for men, older age (40+ yr), low income, and with comorbid chronic heart disease, chronic lung disease, impaired immune disease, chronic renal disease, stroke, and cancer, and for those requiring invasive or noninvasive respiratory supports, who developed septic shock or had organ failures ( p < 0.05). In contrast, foreign-born patients, those with booster vaccine, and those who had taken steroids had better survival (aHR = 0.87; 95% CI, 0.80-0.95; 0.74, 0.65-0.84, and 0.91, 0.84-0.98, respectively). Observed associations were similar across different variant periods. CONCLUSIONS: In this nationwide Swedish cohort covering over two and a half years of the pandemic, ICU survival rates changed over time. Older age was a strong predictor across all periods. Furthermore, most other mortality predictors remained consistent across different variant periods.

Unit-to-unit transfer due to shortage of intensive care beds in Sweden 2015-2019 was associated with a lower risk of death but a longer intensive care stay compared to no transfer: a registry study.

BACKGROUND: Intensive care unit-to-unit transfer due to temporary shortage of beds is increasing in Sweden. Transportation induces practical hazards, and the change of health care provider may prolong the length of stay in intensive care. We previously showed that the risk of death at 90 days did not differ between patients transferred due to a shortage of beds and non-transferred patients with a similar burden of illness in a tertiary intensive care unit. The aim of this study was to widen the analysis to a nation-wide cohort of critically ill patients transferred to another intensive care unit in Sweden due to shortage of intensive care beds. METHODS: Retrospective comparison between capacity transferred and non-transferred patients, based on data from the Swedish Intensive Care Registry during a 5-year period before the COVID-19 pandemic. Patients with insufficient data entries or a recurring capacity transfer within 90 days were excluded. To assess the association between capacity transfer and death as well as intensive care stay within 90 days after ICU admission, logistic regression models with step-wise adjustment for SAPS3 score, primary ICD-10 ICU diagnosis and the number of days in the intensive care unit before transfer were applied. RESULTS: From 161,140 eligible intensive care admissions, 2912 capacity transfers were compared to 135,641 discharges or deaths in the intensive care unit. Ninety days after ICU admission, 28% of transferred and 21% of non-transferred patients were deceased. In the fully adjusted model, capacity transfer was associated with a lower risk of death within 90 days than no transfer; OR (95% CI) 0.71 (0.65-0.69) and the number of days spent in intensive care was longer: 12.4 [95% CI 12.2-12.5] vs 3.3 [3.3-3.3]. CONCLUSIONS: Intensive care unit-to-unit transfer due to shortage of bed capacity as compared to no transfer during a 5-year period preceding the COVID-19 pandemic in Sweden was associated with lower risk of death within 90 days but with longer stay in intensive care.

End-of-life decision-making in critically ill old patients with and without coronavirus disease 2019.

BACKGROUND: There are few studies on the differences in end-of-life decisions making in critically ill patients with and without coronavirus disease 2019 (COVID-19). This study aimed to investigate the independent factors that predicted the decision to withdraw or withhold life-sustaining treatments (LST) in critically ill patients and if these decisions were based on different variables for critically ill patients with COVID-19 compared to those for critically ill patients with other diagnoses in a Swedish intensive care unit. METHODS: This observational pilot study was performed at Sahlgrenska University Hospital, Gothenburg, Sweden. Patients ≥65 years were included from 1 March 2020 to 30 April 2021. The association between a decision to limit LST and a priori selected variables including sex, age, Simplified Acute Physiology Score 3 (SAPS 3), Clinical Frailty Scale ≥4, Charlson Comorbidity Index, Body Mass Index, living at home, invasive and non-invasive mechanical ventilation was assessed using a univariate and multivariable logistic regression model and presented as odds ratio with corresponding 95% confidence intervals. RESULTS: There were 394 patients included in this study, 131 in the non-COVID-19 group and 263 in the COVID-19 group. For the non-COVID-19 cohort, the univariate analysis demonstrated that age and SAPS 3 were significantly associated with the decision to withdraw or withhold life-sustaining treatments, and this association remained in the multivariable analysis, with odds ratios of 1.10 (1.03-1.19) p = .009 and 1.06 (1.03-1.10) p < .001, respectively. For the COVID-19 cohort, the univariate analysis indicated that age, SAPS 3, and Charlson comorbidity index were significantly associated with the decision to withdraw or withhold life-sustaining treatments. However, in multivariable analysis, only the Charlson comorbidity index remained independently associated with the decision to withdraw or withhold life-sustaining treatments, with an odds ratio of 1.26 (1.07-1.49), p = .006. CONCLUSION: Decisions to withdraw or withhold life-sustaining treatments were based on other variables for the critically ill COVID-19 cohort compared to those for the critically ill non-COVID-19 cohort. Further studies are warranted to forge a common path for ethical end-of-life decision-making in critically ill patients.

Hypotension during transsphenoidal pituitary surgery associated with increase in plasma levels of brain injury markers.

BACKGROUND: Patients undergoing pituitary surgery may experience short- and long-term postoperative morbidity. Intraoperative factors such as hypotension might be a contributing factor. Our aim was to investigate the association between intraoperative hypotension and postoperative plasma levels of tau, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) as markers of perioperative brain injury. METHODS: Between June 2016 and October 2017, 35 patients from the Gothenburg Pituitary Tumor Study were included. For tau, NfL, and GFAP, concentrations were measured in plasma samples collected before and immediately following surgery, and on postoperative days 1 and 5. The difference between the highest postoperative value and the value before surgery was used for analysis (∆taupeak , ∆NfLpeak , ∆GFAPpeak ). Intraoperative hypotension was defined as the area under the curve of an absolute threshold below 70 mmHg (AUC70) and a relative threshold below 20% (AUC20%) of the baseline mean arterial blood pressure. RESULTS: Plasma tau and GFAP were highest immediately following surgery and on day 1, while NfL was highest on day 5. There was a positive correlation between AUC20% and both ∆taupeak (r2 = .20, p < .001) and ∆NfLpeak (r2 = .26, p < .001). No association was found between AUC20% and GFAP or between AUC70 and ∆taupeak , ∆NfLpeak or ∆GFAPpeak . CONCLUSION: Intraoperative relative, but not absolute, hypotension was associated with increased postoperative plasma tau and NfL concentrations. Patients undergoing pituitary surgery may be vulnerable to relative hypotension, but this needs to be validated in future prospective studies.

Validating a Simplified Lung Ultrasound Protocol for Detection and Quantification of Pulmonary Edema in Patients With Chronic Kidney Disease Receiving Maintenance Hemodialysis.

OBJECTIVES: Pulmonary edema is a common clinical problem and lung ultrasound (LUS) presents an efficient method for evaluating this pathology. This study aims to investigate if a clinically efficient LUS protocol can quantify the level of extravascular lung fluid in patients receiving hemodialysis, and to develop a simplified B-line scoring system based on this protocol. METHODS: A simple 8-area LUS approach was used for the assessment of the extravascular fluid status in patients before, during, and after receiving hemodialysis. The LUS assessments were compared to the amount of removed fluid over time. To determine the best B-line score system, different scorings for each zone were tested in a linear mixed model with pseudo R-square model fit against removed fluid. The B-line score was further validated through correlations with changes in oxygen saturation, grade of dyspnea, and body weight over time. RESULTS: A total of 53 patients were included and examined on 108 hemodialysis occasions. Median fluid removal was 2.3 L. The B-line score model with best fit was a score of 0 points in a zone with 0 or 1 B-lines, 1 point with 2 or 3 B-lines, 2 points with 3 or more B-lines, and 3 points with any interstitial confluence. Using this B-line score, we found a significant association with amount of removed fluid, oxygen saturation, grade of dyspnea, and change in body weight. CONCLUSION: A straightforward protocol for LUS and B-line score system was shown valid for quantification of pulmonary edema and fluid removal in hemodialysis patients. The scoring system developed here can be useful also in other patient groups, but this requires further validation.

Isolated diastolic dysfunction is associated with increased mortality in critically ill patients.

PURPOSE: Left ventricular (LV) diastolic dysfunction is important in critically ill patients, but prevalence and impact on mortality is not well studied. We classified intensive care patients with normal left ventricular function according to current diastolic guidelines and explored associations with mortality. MATERIAL AND METHODS: Echocardiography was performed within 24 h of intensive care admission. Patients with reduced LV ejection fraction, regional wall motion abnormality, or a history of cardiac disease were excluded. Patients were classified according to the 2016 EACVI guidelines, Recommendations for the Evaluation of LV Diastolic Function by Echocardiography. RESULTS: Out of 218 patients, 162 (74%) had normal diastolic function, 21 (10%) had diastolic dysfunction, and 35 (17%) had indeterminate diastolic function. Diastolic dysfunction were more common in female patients, older patients and associated with sepsis, respiratory and cardiovascular comorbidity as well as higher SAPS Score. In a risk-adjusted logistic regression model, patients with indeterminate diastolic dysfunction (OR 4.3 [1.6-11.4], p = 0.004) or diastolic dysfunction (OR 5.1 [1.6-16.5], p = 0.006) had an increased risk of death at 90 days compared to patients with normal diastolic function. CONCLUSION: Isolated diastolic dysfunction, assessed by a multi-parameter approach, is common in critically ill patients and is associated with mortality. TRIAL REGISTRATION: Secondary analysis of data from a single-center prospective observational study focused on systolic dysfunction in intensive care unit patients (Clinical Trials ID: NCT03787810.

RWMAs in critically ill patients with non-obstructed coronary arteries.

INTRODUCTION: Left ventricular (LV) dysfunction is estimated to occur in 10%-25% of the general intensive care unit (ICU) population and is frequently seen as regional wall motion abnormalities (RWMAs). Although RWMA is mostly attributed to myocardial ischemia or infarction, some studies have suggested that nonischemic RWMA might also be prevalent. We sought to establish that RWMA can be seen in critically ill patients with normal coronary arteries and to explore reasons for RWMA in this population. METHODS: In this retrospective study, data from the hospital angiography register and the ICU register were collated between 2012 and 2019. Patients were identified who underwent angiography in conjunction with their ICU stay and had RWMA on echocardiography. Patients were divided into either those with non-obstructed or those with obstructed coronary arteries. Cardiac magnetic resonance imaging (cMRI) examinations were reviewed if they had been performed on patients with non-obstructed coronaries. RESULTS: We identified 53 patients with RWMA and non-obstructed coronary arteries and 204 patients with RWMA and obstructed coronary arteries. Patients with non-obstructed coronary arteries were more often female, younger, and had fewer cardiovascular risk factors. They less commonly had ST elevation, but more frequently had T-wave inversion or serious arrhythmias. Troponin levels were higher in patients with obstructed coronary arteries, but NT-proBNP was similar between the groups. There were no differences in risk-adjusted 90-day mortality between patients with non-obstructed versus obstructed coronary arteries (OR 1.21, [95% CI 0.56-2.64], p = .628). In those with non-obstructed coronary arteries, follow-up echocardiography was available for 38 patients, of whom 30 showed normalization of cardiac function. Of the 14 patients with non-obstructed coronary arteries on whom cMRI was performed, 7 had a tentative diagnosis of Takotsubo syndrome or myocardial stunning; 4 had a myocardial infarction (preexisting in 3 cases); 1 patient had acute myocarditis; 1 patient had post-myocarditis; and 1 patient was diagnosed with dilated cardiomyopathy. CONCLUSION: RWMA can be seen to occur in critically ill patients in the absence of coronary artery obstruction. Several conditions can cause regional hypokinesia, and cMRI is useful to evaluate the underlying etiology.

Protocolised reduction of non-resuscitation fluids versus usual care in patients with septic shock (REDUSE): a protocol for a multicentre feasibility trial.

INTRODUCTION: Administration of large volumes of fluids is associated with poor outcome in septic shock. Recent data suggest that non-resuscitation fluids are the major source of fluids in the intensive care unit (ICU) patients suffering from septic shock. The present trial is designed to test the hypothesis that a protocol targeting this source of fluids can reduce fluid administration compared with usual care. METHODS AND ANALYSIS: The design will be a multicentre, randomised, feasibility trial. Adult patients admitted to ICUs with septic shock will be randomised within 12 hours of admission to receive non-resuscitation fluids either according to a restrictive protocol or to receive usual care. The healthcare providers involved in the care of participants will not be blinded. The participants, outcome assessors at the 6-month follow-up and statisticians will be blinded. Primary outcome will be litres of fluids administered within 3 days of randomisation. Secondary outcomes will be proportion of randomised participants with outcome data on all-cause mortality; days alive and free of mechanical ventilation within 90 days of inclusion; any acute kidney injury and ischaemic events in the ICU (cerebral, cardiac, intestinal or limb ischaemia); proportion of surviving randomised patients who were assessed by European Quality of Life 5-Dimensions 5-Level questionnaire and Montreal Cognitive Assessment; proportion of all eligible patients who were randomised and proportion of participants experiencing at least one protocol violation. ETHICS AND DISSEMINATION: Ethics approval has been obtained in Sweden. Results of the primary and secondary outcomes will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05249088.

Long-term outcomes after aneurysmal subarachnoid hemorrhage: A prospective observational cohort study.

OBJECTIVES: The survival rates for patients affected by aneurysmal subarachnoid hemorrhage (aSAH) have increased in recent years; however, many patients continue to develop cognitive dysfunctions that affect their quality of life. The commonly used outcome measures often fail to identify these cognitive dysfunctions. This study aimed to evaluate the long-term outcomes at 1 and 3 years after aSAH to assess changes over time and relate outcomes to patient characteristics and events during the acute phase. MATERIALS AND METHODS: This prospective observational study included patients that experienced aSAH. Patients were assessed according to the extended Glasgow Outcome Scale, Life Satisfaction Questionnaire, Mayo-Portland Adaptability inventory-4, and Mental Fatigue scale. RESULTS: Patients were assessed after 1 year (n = 62) and 3 years (n = 54). At 3 years, the extended Glasgow Outcome Scale score improved in 15% and worsened in 12% of the patients. Mental fatigue was observed in 57% of the patients at 1 year. Patients <60 years of age at the time of aSAH had more self-assessed problems, including pain/headache (p < .01), than patients >60 years of age. Patients with delayed cerebral ischemia during the acute phase reported more dissatisfaction at 3 years, whereas no significant result was seen at 1 year. CONCLUSIONS: Cognitive dysfunction, especially mental fatigue, is common in patients with aSAH, which affects quality of life and recovery. Patient outcome is a dynamic process developing throughout years after aSAH, involving both improvement and deterioration. This study indicates the importance of longer follow-up periods with broad outcome assessments.

Cardiac dysfunction and mortality in critically ill patients with COVID-19: A Swedish multicentre observational study.

BACKGROUND: The prevalence and importance of cardiac dysfunction in critically ill patients with COVID-19 in Sweden is not yet established. The aim of the study was to assess the prevalence of cardiac dysfunction and elevated pulmonary artery pressure (PAP), and its influence on mortality in patients with COVID-19 in intensive care in Sweden. METHODS: This was a multicentre observational study performed in five intensive care units (ICUs) in Sweden. Patients admitted to participating ICU with COVID-19 were examined with echocardiography within 72 h from admission and again after 4 to 7 days. Cardiac dysfunction was defined as left ventricular (LV) dysfunction (ejection fraction <50% and/or regional hypokinesia) or right ventricular (RV) dysfunction (defined as TAPSE <17 mm or visually assessed moderate/severe RV dysfunction). RESULTS: We included 132 patients, of whom 127 (96%) were intubated. Cardiac dysfunction was found in 42 (32%) patients. Most patients had cardiac dysfunction at the first assessment (n = 35) while a few developed cardiac dysfunction later (n = 7) and some changed type of dysfunction (n = 3). LV dysfunction was found in 21 and RV dysfunction in 19 patients, while 5 patients had combined dysfunction. Elevated PAP was found in 34 patients (26%) and was more common in patients with RV dysfunction. RV dysfunction and elevated PAP were independently associated with an increased risk of death (OR 3.98, p = .013 and OR 3.88, p = .007, respectively). CONCLUSIONS: Cardiac dysfunction occurs commonly in critically ill patients with COVID-19 in Sweden. RV dysfunction and elevated PAP are associated with an increased risk of death.

Study protocol: establishment of a multicentre pre-eclampsia database and biobank in Sweden: GO PROVE and UP MOST, a prospective cohort study.

INTRODUCTION: Pre-eclampsia, a multisystem disorder in pregnancy, is one of the most common causes of maternal morbidity and mortality worldwide. However, we lack methods for objective assessment of organ function in pre-eclampsia and predictors of organ impairment during and after pre-eclampsia. The women's and their partners' experiences of pre-eclampsia have not been studied in detail. To phenotype different subtypes of the disorder is of importance for prediction, prevention, surveillance, treatment and follow-up of pre-eclampsia.The aim of this study is to set up a multicentre database and biobank for pre-eclampsia in order to contribute to a safer and more individualised treatment and care. METHODS AND ANALYSIS: This is a multicentre cohort study. Prospectively recruited pregnant women ≥18 years, diagnosed with pre-eclampsia presenting at Sahlgrenska University Hospital, Uppsala University Hospital and at Södra Älvsborgs Hospital, Sweden, as well as normotensive controls are eligible for participation. At inclusion and at 1-year follow-up, the participants donate biosamples that are stored in a biobank and they are also asked to participate in various organ-specific evaluations. In addition, questionnaires and interviews regarding the women's and partner's experiences are distributed at follow-up. ETHICS AND DISSEMINATION: By creating a database and biobank, we will provide the means to explore the disorder in a broader sense and allow clinical and laboratory discoveries that can be translated to clinical trials aiming at improved care of women with pre-eclampsia. Further, to evaluate experiences and the psychological impact of being affected by pre-eclampsia can improve the care of pregnant women and their partners. In case of incidental pathological findings during examinations performed, they will be handled in accordance with clinical routine. Data are stored in a secure online database. Biobank samples are identified through the women's personal identification number and pseudonymised after identification in the biobank before analysis.This study was approved by the regional ethical review board in Gothenburg on 28 December 2018 (approval number 955-18) and by the Swedish Ethical Review Authority on 27 February 2019 (approval number 2019-00309).Results from the study will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN13060768.

Regional left ventricular systolic dysfunction associated with critical illness: incidence and effect on outcome.

AIMS: Left ventricular (LV) dysfunction can be triggered by non-cardiac disease, such as sepsis, hypoxia, major haemorrhage, or severe stress (Takotsubo syndrome), but its clinical importance is not established. In this study, we evaluate the incidence and impact on mortality of LV dysfunction associated with critical illness. METHODS AND RESULTS: In this single-centre, observational study, consecutive patients underwent an echocardiographic examination within 24 h of intensive care unit (ICU) admission. LV systolic dysfunction was defined as an ejection fraction (EF) < 50% and/or regional wall motion abnormalities (RWMA). A cardiologist assessed patients with LV dysfunction for the presence of an acute or chronic cardiac disease, and coronary angiography was performed in high-risk patients. Of the 411 patients included, 100 patients (24%) had LV dysfunction and in 52 (13%) of these patients, LV dysfunction was not attributed to a cardiac disease. Patients with LV dysfunction and non-cardiac disease had higher mortality risk score (Simplified Acute Physiologic Score 3 score), heart rate, noradrenaline doses, and lactate levels as well as decreased EF, stroke volume, and cardiac output compared with patients with normal LV function. Diagnoses most commonly associated with LV dysfunction and non-cardiac disease were sepsis, respiratory insufficiency, major haemorrhage, and neurological disorders. RWMA (n = 40) with or without low EF was more common than global hypokinesia (n = 12) and was reversible in the majority of cases. Twelve patients had a circumferential pattern of RWMA in concordance with Takotsubo syndrome. Crude 30 day mortality was higher in patients with LV dysfunction and non-cardiac disease compared with patients with normal LV function (33% vs. 18%, P = 0.023), but not after risk adjustment (primary outcome) {odds ratio [OR] 1.56 [confidence interval (CI) 0.75-3.39], P = 0.225}. At 90 days, crude mortality was 44% and 22% (P = 0.002), respectively, in these groups. This difference was also significant after risk adjustment [OR 2.40 (CI 1.18-4.88), P = 0.016]. CONCLUSIONS: Left ventricular systolic dysfunction is commonly triggered by critical illness, is frequently seen as regional hypokinesia, and is linked to an increased risk of death. The prognostic importance of LV dysfunction in critical illness might be underestimated.

Sacubitril/valsartan decreases mortality in the rat model of the isoprenaline-induced takotsubo-like syndrome.

AIMS: Takotsubo syndrome (TTS) is an acute potentially reversible cardiac syndrome characterized by variable regional myocardial akinesia that cannot be attributed to a culprit coronary artery occlusion. TTS is an important differential diagnosis of acute heart failure where brain natriuretic peptides are elevated. Sacubitril/valsartan is a novel and effective pharmacological agent for the treatment of patients with heart failure. Our aim was to explore whether treatment with sacubitril/valsartan could prevent isoprenaline-induced takotsubo-like phenotype in rats. METHODS AND RESULTS: A total number of 186 Sprague-Dawley male rats were randomized to receive pretreatment with water (CONTROL, n = 62), valsartan (VAL, n = 62), or sacubitril/valsartan (SAC/VAL, n = 62) before receiving isoprenaline for induction of TTS. We recorded heart rate and blood pressure invasively. Cardiac morphology and function were evaluated by high-resolution echocardiography 90 min after the administration of isoprenaline. We documented the survival rate at the time of echocardiography. Compared with the CONTROL group, the SAC/VAL group had less pronounced TTS-like cardiac dysfunction and lower mortality rate, while the VAL group did not differ. Heart rate and blood pressure were not significantly different between the groups. Analysis of cardiac lipids was performed with mass spectrometry. The VAL and SAC/VAL groups had significantly higher levels of lysophosphatidylcholine (LPC), in particular LPC 18:1 and LPC 16:0. CONCLUSIONS: Pretreatment with sacubitril/valsartan but not with valsartan reduces mortality and attenuates isoprenaline-induced apical akinesia in the TTS-like model in rats. Sacubitril/valsartan could be a potential treatment option in patients with TTS in humans.